Pima Indians have a high prevalence of obesity, diabetes mellitus and hyperinsulipemia, but they have low plasma cholesterol levels, reduced low density lipoprotein (LDL) synthesis, and decreased incidence of cardiovascular disease. Lipoprotein metabolism in Pima Indians is being investigated in order to further understand control of lipoprotein metabolism in this population and how lipid metabolism is influenced by obesity and diabetes. Simultaneous studies have been performed of very low density lipoprotein (VLDL) apoB and LDL apoB metabolism using a double isotope procedure. Methods have been developed to facilitate isolation of apoB and estimation of plasma volume. In addition, a multicompartmental model has been developed for the analysis of kinetic data for the simultaneous measure of VLDL, IDL and LDL apoB metabolism. Studies in a group of male Pimas indicated that obesity results in a greatly increased flux of VLDL apoB. LDL apoB levels were not elevated in the obese subjects, because of both increased metabolism of VLDL through the alternate pathway and increased catabolism of LDL. Comparison of apoB metabolism in Pimas and weight-matched Causasians indicated that the low LDL in Pimas is related to both higher FCR for LDL and higher proportion of VLDL metabolized without conversion to LDL. Furthermore, VLDL "shunt" and LDL FCR appeared to be correlated. The results of lipoprotein metabolic studies in Pimas to date suggest a large flux of substrates and regulators (i.e. insulin) which cause overproduction of lipoproteins, but that compensatory mechanism are operative which result in maintenance of low plasma concentrations.